1. Field of the Invention
The present invention relates to analysis technology involved in gene sequences in analyses of biologically functional molecules, particularly DNA sequences and in genetic diagnosis, and a method for manufacturing a substrate for making a device for analysis used for those analyses.
2. Description of the Related Art
The analysis technology for DNA sequences of genes including human genomic analysis has been advanced rapidly in recent years, and has been developed for the study on gene functions and diagnosis of diseases by the gene based on that information. Numerous studies on so-called DNA chips, DNA microarrays as the technology for performing these analyses and functional studies of the genes on a large scale in a short time have been performed.
In the DNA microarray, DNA having the particular sequence is immobilized in a microspace and a DNA strand having a complementary sequence in a sample is detected. As a methodology for making the DNA microarray capable of processing on a large scale and with high speed, a method of making the microarray modified with various DNA in surprisingly few steps by performing a position-selective synthesis of DNA sequences over multiple stages using photolithography which is a method for making a semiconductor has been proposed in CHEMTECH February 1997, pp. 22. According to this, a possibility has been shown that the microarray for examining more than one billion DNA sequences at the same time can be make by repeating binding of methodically and position-selectively different nucleotides 15 times.
Meanwhile, if the DNA strand having the above complementary sequence can be electrically detected, it becomes possible to analyze by a high speed and simple method. Domestic Re-publication of WO2003/087798 and Japanese Patent Laid-open (Kokai) No. 2005-77210-A have been already known as attempts to make the microarray using a semiconductor apparatus for the purpose of such an electric detection. In these semiconductor apparatuses, the presence or absence of the complementary DNA strand is detected on a microchip as a practical application of a sensor by a field effect transistor known conventionally.
By the way, to make the DNA microarray capable of analyzing on a large scale and with high speed, it is necessary to immobilize the DNA strand on the substrate for making the microarray position-selectively to the microspace and not to cause problems such as detachment. In order to analyze the biologically functional molecules including DNA molecules, as the method for two-dimensionally immobilizing them on a metal, the method of using specific absorption of a sulfur atom on a gold surface is known and described in, for example, Domestic Re-publication of WO2003/087798. Meanwhile, the method in which a monomolecular film having a silicon oxide chain is formed on the substrate so that the immobilized molecule is not detached and an enzyme is certainly immobilized on the semiconductor, and the enzyme is immobilized on an alkyl chain extending from a silicon atom has been known quite some time ago, and disclosed in Japanese Patent Laid-open (Kokai) No. 62-50657-A. This method is also mentioned to be applicable in Japanese Patent Laid-open (Kokai) No. 2005-77210-A.
For making the microarray, when a material for recognition of such as DNA or a peptide is immobilized on the substrate, the above method of using the monomolecular film having the silicon oxide chain is the method for immobilization in which the above-mentioned problem such as detachment hardly occurs.
But, if this method is used, when actually a oxidized film formed on the substrate although the surface of the substrate is formed of a metal oxide or a metal, the monomolecular film having the silicon oxide chain forms a film on the overall surface.
Thus, when the monomolecular film is placed position-selectively, it is useful to protect with a resist film. However, when a novolak resist used in commonsense for forming a pattern requiring the accuracy in approximately micron orders or a resist for processing the semiconductor developed for KrF excimer having a some excessive miniaturization performance is used, the resist film itself reacts with the material for forming the monomolecular film and the monomolecular film is also formed on the resist film. Thus, extremely complicated manipulations are required for forming the film position-selectively.
Therefore, it is substantially impossible to use such a resist for processing the semiconductor for manufacturing the substrate for making the microarray. A resist technology capable of simply forming the monomolecular film in position-selectively has been desired.